Gpr37 modulates the severity of inflammation-induced GI dysmotility by regulating enteric reactive gliosis

Summary: The enteric nervous system (ENS) is contained within two layers of the gut wall and is made up of neurons and enteric glial cells (EGCs) that regulate gastrointestinal (GI) function. EGCs in both inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) change in response to infla...

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Main Authors: Keiramarie Robertson, Oliver Hahn, Adarsh Tantry, Beatriz G. Robinson, Arwa T. Faruk, Mathangi Janakiraman, Hong Namkoong, Kwangkon Kim, Jiayu Ye, Estelle Spear Bishop, Randy A. Hall, Tony Wyss-Coray, Laren Becker, Julia A. Kaltschmidt
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225011460
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author Keiramarie Robertson
Oliver Hahn
Adarsh Tantry
Beatriz G. Robinson
Arwa T. Faruk
Mathangi Janakiraman
Hong Namkoong
Kwangkon Kim
Jiayu Ye
Estelle Spear Bishop
Randy A. Hall
Tony Wyss-Coray
Laren Becker
Julia A. Kaltschmidt
author_facet Keiramarie Robertson
Oliver Hahn
Adarsh Tantry
Beatriz G. Robinson
Arwa T. Faruk
Mathangi Janakiraman
Hong Namkoong
Kwangkon Kim
Jiayu Ye
Estelle Spear Bishop
Randy A. Hall
Tony Wyss-Coray
Laren Becker
Julia A. Kaltschmidt
author_sort Keiramarie Robertson
collection DOAJ
description Summary: The enteric nervous system (ENS) is contained within two layers of the gut wall and is made up of neurons and enteric glial cells (EGCs) that regulate gastrointestinal (GI) function. EGCs in both inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) change in response to inflammation, referred to as reactive gliosis. Whether EGCs restricted to a specific layer or region within the GI tract alone can influence intestinal immune response is unknown. Using bulk RNA-sequencing and in situ hybridization, we identify G-protein coupled receptor Gpr37, as a gene expressed in EGCs of the myenteric plexus, one of the two layers of the ENS. We show that Gpr37 contributes to key components of LPS-induced reactive gliosis including activation of NF-kB and IFN-y signaling and response genes, lymphocyte recruitment, and inflammation-induced GI dysmotility. Targeting Gpr37 presents a potential avenue for modifying inflammatory processes in the ENS.
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publishDate 2025-07-01
publisher Elsevier
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series iScience
spelling doaj-art-5bca7cf387ad42d1a68ce52a1fcb1f992025-08-20T03:24:20ZengElsevieriScience2589-00422025-07-0128711288510.1016/j.isci.2025.112885Gpr37 modulates the severity of inflammation-induced GI dysmotility by regulating enteric reactive gliosisKeiramarie Robertson0Oliver Hahn1Adarsh Tantry2Beatriz G. Robinson3Arwa T. Faruk4Mathangi Janakiraman5Hong Namkoong6Kwangkon Kim7Jiayu Ye8Estelle Spear Bishop9Randy A. Hall10Tony Wyss-Coray11Laren Becker12Julia A. Kaltschmidt13Neurosciences Graduate Program, Stanford University, Stanford, CA, USA; Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USAWu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA; Department of Neurology and Neurological Sciences, Stanford School of Medicine, Stanford, CA, USANeurosciences Graduate Program, Stanford University, Stanford, CA, USA; Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USANeurosciences Graduate Program, Stanford University, Stanford, CA, USA; Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USADepartment of Human Biology, Stanford University, Stanford, CA, USADepartment of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USADepartment of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USADepartment of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USADepartment of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USADepartment of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USADepartment of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA, USAWu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA; Department of Neurology and Neurological Sciences, Stanford School of Medicine, Stanford, CA, USADepartment of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA; Corresponding authorWu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA; Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Corresponding authorSummary: The enteric nervous system (ENS) is contained within two layers of the gut wall and is made up of neurons and enteric glial cells (EGCs) that regulate gastrointestinal (GI) function. EGCs in both inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) change in response to inflammation, referred to as reactive gliosis. Whether EGCs restricted to a specific layer or region within the GI tract alone can influence intestinal immune response is unknown. Using bulk RNA-sequencing and in situ hybridization, we identify G-protein coupled receptor Gpr37, as a gene expressed in EGCs of the myenteric plexus, one of the two layers of the ENS. We show that Gpr37 contributes to key components of LPS-induced reactive gliosis including activation of NF-kB and IFN-y signaling and response genes, lymphocyte recruitment, and inflammation-induced GI dysmotility. Targeting Gpr37 presents a potential avenue for modifying inflammatory processes in the ENS.http://www.sciencedirect.com/science/article/pii/S2589004225011460NeuroscienceMolecular biologyImmunity
spellingShingle Keiramarie Robertson
Oliver Hahn
Adarsh Tantry
Beatriz G. Robinson
Arwa T. Faruk
Mathangi Janakiraman
Hong Namkoong
Kwangkon Kim
Jiayu Ye
Estelle Spear Bishop
Randy A. Hall
Tony Wyss-Coray
Laren Becker
Julia A. Kaltschmidt
Gpr37 modulates the severity of inflammation-induced GI dysmotility by regulating enteric reactive gliosis
iScience
Neuroscience
Molecular biology
Immunity
title Gpr37 modulates the severity of inflammation-induced GI dysmotility by regulating enteric reactive gliosis
title_full Gpr37 modulates the severity of inflammation-induced GI dysmotility by regulating enteric reactive gliosis
title_fullStr Gpr37 modulates the severity of inflammation-induced GI dysmotility by regulating enteric reactive gliosis
title_full_unstemmed Gpr37 modulates the severity of inflammation-induced GI dysmotility by regulating enteric reactive gliosis
title_short Gpr37 modulates the severity of inflammation-induced GI dysmotility by regulating enteric reactive gliosis
title_sort gpr37 modulates the severity of inflammation induced gi dysmotility by regulating enteric reactive gliosis
topic Neuroscience
Molecular biology
Immunity
url http://www.sciencedirect.com/science/article/pii/S2589004225011460
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